1. Field of the Invention
This invention relates to novel nucleic acid probes and methods and kits for their preparation and use.
2. Background Information
In the biochemical manipulation of nucleic acids it is frequently desirable to isolate particular nucleic acid material from a complex mixture and to subject this to a wide variety of processes. It has been found particularly useful, where a sufficiently long sequence of the target nucleic acid is known, to design an oligonucleotide probe which will hybridise selectively to that sequence and which may then be used in the identification and/or isolation of the nucleic acid. In particular, it has been proposed to immobilise such a probe so that on contact with a complex mixture containing the target nucleic acid, the latter is selectively immobilised and may thus be separated.
It has been proposed to attach oligonucleotides to magnetic particles previously (for example in U.S. Pat. No. 4,672,040 of Advanced Magnetics, EP 265244 of Amoco Corporation). However, these have never been monodisperse and have normally comprised magnetite which has been ground to an appropriate average particle size and then coated with a substance providing functional groups permitting attachment of a range of biomolecules of interest including oligonucleotides. Furthermore, such magnetic particles have proved unreliable particularly in automated reaction systems, and have not found favour in practice. In particular, it has been found that fine magnetic particles produced by grinding often respond inadequately to magnetic aggregation so that a significant fraction remain in suspension, together with attached biomolecules and a less than quantitative isolation of the biomolecules is effected. The present invention is based on the finding that monodisperse, superparamagnetic particles are far more reliable than previously proposed magnetic particles.